Basic Principles of Synthetic Biology
Engineering Biology for Innovation
Magnus Stefansson, MBA, Ph.D.
Applied Biotechnology and Enterprise Program
2025-06-13
Course Overview
Today’s Learning Objectives:
- Define synthetic biology and its core principles
- Understand key engineering approaches in biology
- Explore standardization and modularity concepts
- Examine commercial applications and market potential
- Discuss ethical considerations and future directions
What is Synthetic Biology?
Definition: Engineering approach to biology that applies engineering principles to biological systems
Goal: Design and construct new biological parts, devices, and systems
Approach: Redesign existing natural biological systems for useful purposes
Interdisciplinary field: Combines biology, engineering, computer science, and chemistry
Bottom-up construction: Building biological systems from well-characterized parts
Source: Nature Reviews Molecular Cell Biology (2016)
Historical Context and Key Milestones
Key Milestones:
1970s: Recombinant DNA technology foundations
2000: First synthetic genome (φX174 bacteriophage)
2003: BioBricks and standardized parts concept
2010: First synthetic bacterial genome (Mycoplasma mycoides)
2016: Synthetic yeast chromosome project
2020s: CRISPR integration and advanced gene circuits
Core Principle 1: Engineering Design Cycle
Traditional Engineering Approach:
- Design: Specify system requirements
- Build: Construct the system
- Test: Measure performance
- Learn: Analyze results and iterate
Applied to Biology:
- Design: Define biological function
- Build: Assemble genetic circuits
- Test: Measure biological output
- Learn: Optimize and redesign
Source: Nature Biotechnology (2018)
Core Principle 2: Standardization
- BioBricks: Standardized biological parts with defined interfaces
- RFC Standards: Request for Comments defining part specifications
- Interchangeable components: Parts that work together predictably
- Characterization: Quantitative description of part behavior
- Registries: Databases of characterized biological parts
Source: iGEM Foundation, Registry of Standard Biological Parts
Core Principle 3: Modularity
Hierarchical Organization:
- Parts: Basic functional units (promoters, genes, terminators)
- Devices: Combinations of parts with specific functions
- Systems: Multiple devices working together
- Chassis: Host organisms containing the systems
AI-generated modular system diagram
Core Principle 4: Abstraction
- Physical Layer: DNA sequences, proteins, metabolites
- Device Layer: Functional units (sensors, actuators, logic gates)
- System Layer: Complete biological programs
- Application Layer: Real-world functions and purposes
- Benefit: Enables specialists to work at different levels without understanding all details
Source: Molecular Systems Biology (2017)
Genetic Circuits and Logic Gates
Boolean Logic in Biology:
- AND gates: Multiple inputs required
- OR gates: Any input sufficient
- NOT gates: Inverter circuits
- Toggle switches: Bistable systems
- Oscillators: Periodic behavior
Applications:
- Biosensors for environmental monitoring
- Therapeutic circuits in medicine
- Metabolic pathway control
- Cell fate determination
Source: Science (2013) - Genetic logic circuits
Chassis Organisms
- Escherichia coli: Most common, well-characterized, fast growth
- Saccharomyces cerevisiae: Eukaryotic system, post-translational modifications
- Bacillus subtilis: Gram-positive, protein secretion capabilities
- Pichia pastoris: High protein expression levels
- Mammalian cells: Complex protein folding, human-compatible
- Minimal cells: Reduced genomes for predictable behavior
AI-generated comparison of different chassis organisms
CRISPR Integration in Synthetic Biology
- Programmable gene editing: Precise DNA modifications
- CRISPRa/CRISPRi: Activation and interference systems -Base editing: Single nucleotide changes without double-strand breaks
- Prime editing: Precise insertions, deletions, and substitutions
- Multiplexed editing: Simultaneous modification of multiple targets
Source: Nature Reviews Genetics (2020)
Protein Design and Engineering
- Directed evolution: Laboratory-based protein evolution
- Rational design: Structure-based protein modification
- De novo design: Creating proteins from scratch
- Protein-protein interactions: Engineering binding specificity
- Allosteric regulation: Designing responsive proteins
Source: Nature Chemical Biology (2018)
Biosafety and Containment
Physical Containment:
Laboratory biosafety levels
Specialized equipment and facilities
Training and protocols
Waste management procedures
Biological Containment:
- Auxotrophic strains (nutrient dependencies)
- Kill switches and terminator genes
- Orthogonal biological systems
- Genetic firewalls
AI-generated biosafety illustration
Commercial Example 1: Ginkgo Bioworks
Business Model:
- “Organism company” - designs custom microbes
- Automated strain engineering platform
- Applications in pharmaceuticals, agriculture, food
- Partnerships with major corporations
- Valuation: $15+ billion (2021)
Key Technologies:
- High-throughput DNA assembly
- Automated testing and optimization
- Machine learning for design
- Standardized biological parts
Source: Ginkgo Bioworks company materials
Commercial Example 2: Synthetic Spider Silk
- Companies: Bolt Threads, Spiber, Modern Meadow
- Product: Recombinant spider silk proteins in microorganisms
- Properties: Stronger than steel, biodegradable, lightweight
- Applications: Textiles, medical devices, protective equipment
- Market potential: $1.3 billion by 2027
Source: Nature Materials (2019)
Commercial Example 3: Biofuels and Chemicals
Zymergen (acquired by Ginkgo):
- Microbial strain optimization
- Machine learning-guided engineering
- Focus on specialty chemicals
Amyris:
- Synthetic artemisinin production
- Renewable chemicals from sugar
- Cosmetics and fragrance ingredients
AI-generated biofuel production flowchart
Commercial Example 4: Synthetic Biology in Medicine
- CAR-T cell therapy: Engineered immune cells for cancer treatment
- Biosynthetic insulin: Recombinant human insulin production
- Synthetic antibiotics: Novel antimicrobial compounds
- Personalized medicine: Tailored therapeutic approaches
- Market size: $39 billion by 2027
Source: Nature Biotechnology (2020)
Commercial Example 5: Food and Agriculture
Applications:
- Impossible Foods: Plant-based meat with synthetic heme
- Perfect Day: Animal-free dairy proteins
- Motif FoodWorks: Designer food ingredients
- Crop enhancement: Improved yield and nutrition
Benefits:
- Reduced environmental impact
- Enhanced nutritional content
- Novel flavors and textures
- Sustainable production
AI-generated sustainable food production ::::::::::::::::::::::::::::::::::::::
